Is ENTREP1 p.Ser553= (c.1659G>A) pathogenic?

ENTREP1 p.Ser553= (c.1659G>A) is classified Likely benign in ENTREP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-19). Very rare (popmax 0.00517%, nfe).

How common is ENTREP1 p.Ser553= (c.1659G>A) in the general population?

ENTREP1 p.Ser553= (c.1659G>A) is very rare (popmax 0.00517%, nfe) (gnomAD).

ENTREP1 p.Ser553=

c.1659G>A · rs776945946 · VCV514694

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00517%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7	GERP -3.4
Overall
CADD	0.846	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00517% European (non-Finnish) · 61/1,180,012 alleles

Filtering AF 0.0041% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00372%

Overall 0.00397% 64/1,613,954 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00517%	19,344
Remaining individualsnot grpmax-eligible	0.0016%	62,486
Finnishnot grpmax-eligible	0.00156%	64,014
African / African-American	0.00134%	74,888

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ENTREP1
Protein: p.Ser553=
Coding: c.1659G>A
MANE Select: NM_001347995
dbSNP: rs776945946
Type: single nucleotide variant
Location: chr9:69391651 (GRCh38)
Structure: AlphaFold pLDDT 60.47

Full ENTREP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ENTREP1 p.Ser553Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
ENTREP1 p.Ala374Ser Uncertain significance ★ ⚠ same type
ENTREP1 p.Ala418Asp Uncertain significance ★ ⚠ same type
ENTREP1 p.Ala440Ser Uncertain significance ★ ⚠ same type
ENTREP1 p.Ala440Thr Uncertain significance ★ ⚠ same type
ENTREP1 p.Ala448Ser Uncertain significance ★ ⚠ same type
ENTREP1 p.Ala492Val Uncertain significance ★ ⚠ same type
ENTREP1 p.Ala574Pro Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/entrep1-p-ser553 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown